The factors which initiate lymphocyte accumulation in the lung and the mechanisms by which they migrate are still poorly understood. Our current knowledge suggests that of the many possible sources, the aleveolar macrophage and the lymphocyte may make important contributions in generating chemoattractant activity for T lymphocytes. Therefore we have chosen first to study potential mechanisms of activating alveolar macrophages to produce lymphocyge chemoattractant products. Alveolar macrophages obtained by bronchoalveolar lavage will be placed in culture and stimuli (asbestos, antigens, mitogens, phagocytic particles and lipopolysacharide) capable of activating macrophages will be tested. Lymphocyte chemoattractant activity will be characterized regarding responding cell types (T vs B, Thelper vs T suppressor, etc.), chemical nature (lipid vs protein) and pathways of generation (arachidonic acid metabolism vs protein synthesis). Secondly, we have recently described two human lymphokines which alter lymphocyte migration, and plan to study their mechanisms of action in depth. The chemokinetic factor (LCF) has been purified by us and thus our studies will be directed at characterizing its T lymphocyte receptor, determining its cell of origin and the cell population(s) that respond to it. The second lymphokine (LMIF) is a non-cytotoxic, reversible inhibitor of T cell migration. Our studies will first chemically characterize it, attempt to purify it, determine its cell of origin and mechanism of action. Our experiments will be performed in vitro utilizing cells entirely of human sources; alveolar macrophages will be obtained by bronchoalveolar lavage, and lymphocytes will be obtained from the blood of normal volunteers. Chemoattractant products of these cells will be characterized chemically and their ability to alter lymphocyte migration will be assessed in specially modified miniature Boyden chambers utilizing human blood lymphocyte subsets as the responding target cells. Our objectives are to determine the alveolar macrophage and lymphocyte dependent mechanisms of non-sensitized T lymphocy te migration and accumulation. We hope to later extrapolate this information to the study of patients with fibrotic lung diseases. Our ultimate goal is to learn to modify thy lymphocyte inflammatory response in the lung in active disease processes in a way that is beneficial to the host.